目的 比較砂生槐子總生物堿水劑和片劑的體內(nèi)外性質(zhì)。方法 將砂生槐子制備成總生物堿浸膏，再用生理鹽水稀釋成水劑；通過體外黏附力考察篩選出生物黏附材料海藻酸鈉、卡波姆的最佳比例，制備砂生槐子總生物堿生物黏附片。采用體外pH轉(zhuǎn)換兩步（pH值分別為1.4、6.5）溶出實驗評價砂生槐子總生物堿水劑和片劑在胃腸道中的擴散行為。將20只SD大鼠隨機分為2組，每組10只，分別ig給予砂生槐子總生物堿片劑和水劑，給藥劑量均為7 mg·kg⁻¹，于給藥后0.25、0.50、1.00、2.00、3.00、4.00、5.00、6.00、8.00、10.00、12.00、24.00、36.00、48.00 h取血200～400 μL于EDTA-Na₂制備好的離心管中，分離血漿，超高效液相色譜（UHPLC）法檢測苦參堿、氧化苦參堿、槐定堿的質(zhì)量濃度。結(jié)果 海藻酸鈉與卡波姆的比例為2∶1時，離體腸組織的黏附力最大，為（563.43±20.38）N。體外pH轉(zhuǎn)換溶出實驗顯示水劑進入模擬胃液后迅速擴散；片劑在模擬胃液（pH＝1.4）中幾乎不溶解，模擬腸液（pH＝6.5）中迅速溶解釋放，1 h的累積溶出率在75%以上。藥動學實驗表明，水劑組的苦參堿、氧化苦參堿、槐定堿的峰濃度（C_max）分別是片劑組的2.2、1.9、2.4倍；水劑組各生物堿的達峰時間（t_max）均顯著小于片劑組（P＜0.05）；水劑組氧化苦參堿的血藥濃度-時間曲線下面積AUC_0-∞是片劑組的2.5倍、槐定堿的AUC_0-∞是片劑組的3.5倍。結(jié)論 砂生槐子生物堿水劑體外迅速擴散，體內(nèi)生物利用度優(yōu)于片劑。

Objective The purpose of this study was to compare the in vivo and in vitro properties of different formulations of the total alkaloids of Sophora moocrorftiana. Method Sophora moocrorftiana seeds was prepared into an extract, which is then diluted with physiological saline to form an aqueous solution. The best ratio of bioadhesive materials was screened out through in vitro adhesion investigation, and the total alkaloid bioadhesive tablets of Sophora moocrorftiana were prepared. The in vitro pH conversion dissolution test was used to evaluate the diffusion behavior of different preparations in the gastrointestinal tract. Twenty SD rats were randomly divided into two groups with ten rats in each group. They were given total alkaloid tablets and water intragaigally at the dose of 7.0 mg·kg⁻¹, respectively. At 0.25, 0.50, 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00 h after administration, blood was collected from 200 to 400 μL in a centrifuge tube prepared by EDTA-Na₂ for plasma separation. The mass concentrations of matrine, oxymatrine and sophoridine were determined by UHPLC. Result When the ratio of the adhesive material sodium alginate to carbomer was 2 : 1, the adhesion force of the isolated intestinal tissue was the largest, which was (563.43 ± 20.38) N. The in vitro pH conversion dissolution test showed that the aqueous solution diffused rapidly after entering the simulated gastric juice; the tablet was almost insoluble in the simulated gastric juice (pH = 1.4), and the drug was quickly dissolved and released in the simulated intestinal juice (pH = 6.5). The cumulative dissolution rate of 1h was 75% above. In vivo oral bioavailability experiments showed that the peak concentrations of matrine, oxymatrine, and sophoridine in the liquid group were 2.2, 1.9, and 2.4 times that of the tablet group, respectively. The peak time T_max of each alkaloid in the liquid group was less than that of the tablet group (P < 0.05). The AUC_(0-∞) of oxymatrine of the total alkaloids of Sophora moocrorftiana was 2.5 times that of the tablet group, and the AUC_(0-∞) of sophoridine of the water group was 3.5 times that of the tablet group. Conclusion Sophora moocrorftiana alkaloids in water spread rapidly in vitro, and the bioavailability in vivo was better than that of tablets.

R944

國家自然科學基金資助項目（81960641）；青海大學青年基金項目團隊資助（2020-QYY-1）